Rett syndrome is a neurodevelopmental disorder characterized by cognitive impairment, communication dysfunction, stereotypic movement disorder, and growth failure. Rett syndrome is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment.

A mouse experimental model of Rett syndrome created by genetic invalidation of the MECP2 gene is available. It had been then observed that adult MECP2-deficient mice show respiratory alterations and found that endogenous noradrenaline helps to maintain a normal respiratory rhythm. Desipramine, a selective inhibitor of norepinephrine reuptake, seems to be efficient to reduce the respiratory alteration occuring in MECP2-deficient mice (Insem patent 2005, Villard and Roux 2006).

The aim of the study is to evaluate these obtained results in MECP2-deficient mice on patients with Rett syndrome.

12 patients with Rett syndrome receiving a daily dose of desipramine correlated with the weight :

From 15 to 25 kg : 50 mg ;

From 26 to 35 kg : 75 mg ;

From 36 to 45 kg : 100 mg ;

> 46 kg : 150 mg.

Drug: Administration of a high dose of desipramine

Administration of a daily dose of desipramine correlated with the patient's weight :

From 15 to 25 kg : 50 mg ;

From 26 to 35 kg : 75 mg ;

From 36 to 45 kg : 100 mg ;

> 46 kg : 150 mg.

Experimental: Desipramine low dose

12 patients with Rett syndrome receiving a daily dose of desipramine correlated with the weight :

From 15 to 25 kg : 25 mg ;

From 26 to 35 kg : 50 mg ;

From 36 to 45 kg : 75 mg ;

> 46 kg : 100 mg.

Drug: Administration of a low dose of desipramine

Administration of a daily dose of desipramine correlated with the patient's weight :

From 15 to 25 kg : 25 mg ;

From 26 to 35 kg : 50 mg ;

From 36 to 45 kg : 75 mg ;

> 46 kg : 100 mg.

Placebo Comparator: Placebo

12 patients with Rett syndrome receiving a daily dose of placebo.

Drug: Administration of a placebo

Administration of a daily dose of placebo

Detailed Description:

Rett syndrome is a neurodevelopmental disorder characterized by cognitive impairment, communication dysfunction, stereotypic movement disorder, and growth failure. The diagnosis of Rett syndrome is based on consensus clinical criteria. Rett syndrome is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment.

Only one randomized study versus placebo has been published about a treatment by naltrexone including 25 patients. A light improvement of respiratory parameters was then observed with a deterioration of the cognitive function (Percy, 2004).

A mouse experimental model of Rett syndrome created by genetic invalidation of the MECP2 gene is available. It had been then observed that adult MECP2-deficient mice show respiratory alterations and found that endogenous noradrenaline helps to maintain a normal respiratory rhythm. Desipramine, a selective inhibitor of norepinephrine reuptake, seems to be efficient to reduce the respiratory alteration occuring in MECP2-deficient mice (Insem patent 2005, Villard and Roux 2006).

The aim of the study is to evaluate these obtained results in MECP2-deficient mice on patients with Rett syndrome.

Eligibility

Ages Eligible for Study:

4 Years to 18 Years

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Rett syndrome;

Girls weighing less than 60 kg;

Respiratory alteration;

Diagnosis of Rett syndrome confirmed by MECP2 genotyping (Xq28).

Exclusion Criteria:

Boys;

Pregnancy and breath feeding;

Case history of status epilepticus;

Patient treated by IMAO or sultopride;

Hepatic or renal failure.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990691